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MHRP scientists have developed novel high-throughput tools to study the genetic composition of populations in Uganda and Tanzania

The last decade has witnessed an explosion of human genetic analyses in different world populations, highlighting similarities and differences among studied groups in diverse geographic areas. Some of the largest genetic differences are located in genes that have the potential of influencing susceptibility to infectious diseases. Of special interest to HIV vaccine developers are sub-Saharan African populations, who have the largest prevalence of HIV worldwide. MHRP has been working in East Africa for more than 10 years, conducting extensive work in cohort development, HIV vaccine research, as well as HIV prevention, care and treatment.

Under the leadership of COL Jerome Kim and Francine McCutchan, PhD, scientists at the Department of Molecular Virology and Pathogenesis have developed novel high-throughput tools to study the genetic composition of populations in Uganda and Tanzania. The implementation of these tools has allowed for rapid advances in our understanding of the genetic complexity in this region.

MHRP’s Dr. Rebecca Koehler and Dr. Gustavo Kijak have co-authored two papers recently published in the journal Tissue Antigens on the genetic diversity of HLA and KIR genes in East Africa. These genes are key determinants of cellular immune responses against HIV and can play a significant role in vaccine efficacy. They recently presented their work on genetic diversity of host restriction genes APOBEC and TRIM5, which have the ability to interfere with key steps in the HIV replication cycle within infected cells at the International AIDS Society Conference on Treatment, Pathogenesis and Prevention in Cape Town, South Africa.

“Until recently, we did not have substantial knowledge of the complexity of human genetic factors that influence HIV infection immune responses in this geographic region, which has been a major obstacle for vaccine development. We observed that East African populations exhibit a much larger degree of genetic diversity than other global groups, which further supports the Out-of-Africa theory (that postulates that modern humans originated in East Africa and migrated out of the continent to populate the world)” says Dr. Koehler. They also found that populations from different countries in East Africa (Tanzania, Kenya and Uganda) shared common patterns of genetic variation. Dr. Kijak noted that “some of these genetic variants, rarely found elsewhere, could provide some level of protection from HIV acquisition or disease progression. Understanding their mechanism of action may help us design better drugs and vaccines.”

Overall, the uniqueness of East African populations and their concordant genetic makeup reinforce the rationale for conducting multi-center vaccine trials in this region.